Article abstract
Nature Medicine 14, 275 - 281 (2008)
Published online: 10 February 2008 | doi:10.1038/nm1710
IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia
Shean J Aujla1, Yvonne R Chan2, Mingquan Zheng1, Mingjian Fei1, David J Askew3, Derek A Pociask1, Todd A Reinhart4, Florencia McAllister1, Jennifer Edeal1, Kristi Gaus4, Shahid Husain5, James L Kreindler1, Patricia J Dubin1, Joseph M Pilewski2, Mike M Myerburg2, Carol A Mason6, Yoichiro Iwakura7 & Jay K Kolls1
Abstract
Emerging evidence supports the concept that T helper type 17 (TH17) cells, in addition to mediating autoimmunity, have key roles in mucosal immunity against extracellular pathogens. Interleukin-22 (IL-22) and IL-17A are both effector cytokines produced by the TH17 lineage, and both were crucial for maintaining local control of the Gram-negative pulmonary pathogen, Klebsiella pneumoniae. Although both cytokines regulated CXC chemokines and granulocyte colony–stimulating factor production in the lung, only IL-22 increased lung epithelial cell proliferation and increased transepithelial resistance to injury. These data support the concept that the TH17 cell lineage and its effector molecules have evolved to effect host defense against extracellular pathogens at mucosal sites.
- Children's Hospital of Pittsburgh, Suite 3765, 3705 Fifth Avenue, Pittsburgh, Pennsylvania 15213, USA.
- Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, 3459 Fifth Avenue, 628 Northwest, Pittsburgh, Pennsylvania 15213, USA.
- University of Pittsburgh Medical Center Newborn Medicine Program, Children's Hospital of Pittsburgh and Magee-Women's Research Institute, 300 Halket Street, Pittsburgh, Pennsylvania 15213, USA.
- Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto Street, Pittsburgh, Pennsylvania 15261, USA.
- Division of Infectious Diseases, Transplant Infectious Disease Unit, University of Pittsburgh Medical Center, 3601 Fifth Avenue, Pittsburgh, Pennsylvania 15213, USA.
- Division of Pulmonary and Critical Care Medicine, Louisiana Health Sciences Center, New Orleans, 1901 Perdido Street, Louisiana 70112, USA.
- Center for Experimental Medicine, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Correspondence to: Jay K Kolls1 e-mail: jay.kolls@chp.edu